DESCRIPTION (from the application): The long-term objectives of this project are to define the changes in knee cartilage mechanical function, morphology, and composition resulting from injury with the specific aims of better evaluating cartilage injury by non-invasive means such as magnetic resonance imaging (MRI), and developing therapeutic strategies such as repair and grafting. Injury to the cartilage of the knee joint is an extremely common problem that crosses all age groups and injury severity levels from high energy sports injury to low impact trauma. In particular, damage to the knee joint meniscus frequently leads to degenerative joint disease, including deterioration of the articular cartilage which is characteristic of osteoarthritis. The research design proposed in this project centers on the canine knee (stifle) joint, and two hypotheses: (1) Meniscus injury or partial excision of the meniscus will lead to diminished mechanical properties and deterioration of articular cartilage, and (2) Repair or reconstruction of a meniscus will delay or diminish degenerative changes in articular cartilage. Meniscal and articular cartilage properties will be analyzed after meniscal injury, after partial meniscal excision, after meniscal repair, and after meniscal grafting with a biologic scaffold. Specifically, analysis will include material properties of articular cartilage, and material properties of grafted, non-grafted, and repaired menisci at three months and one year after injury. The materials properties of the tissues will provide longitudinal and correlative data for interpretation of histologic changes, collagen subtyping, and analysis of synovial fluid biomarkers such as the 3B3+, 3B3-, and 5D4 proteoglycan epitopes at the same time intervals. Finally, and importantly, high resolution MRI (under 100 micron resolution) images will be obtained in the meniscal injury group at one year after injury. The MR images analyzed to create volumetric quantification, curvature analysis, and water composition of meniscus as well as cellular organization, articular cartilage thickness and volume, and collagen organization within the articular cartilage. The continuation of this research beyond this proposal will lead to further development and refinement of knee joint cartilage reconstructive protocols using modern principles of tissue engineering.